1. Field of the Invention
The present invention relates to the fields of organic chemistry and material sciences.
2. Brief Description of Related Technology
The state of the art recognises numerous methods for the functionalisation of surfaces. Such functionalisations are used in order to modify the material properties of the surfaces in a targeted manner. Such functionalisations should be as durable as possible and allow for a highly defined loading of the surface.
In the field of medical technology, special importance is placed on functionalised surfaces. Implants should—by way of example in the dental industry and orthopedics (joint replacement)—be as biocompatible as possible, i.e. by not have, inter alia, having a tendency towards biofouling, not causing any inflammatory reactions and not being seeded with pathogenic microorganisms. Furthermore, they must permanently resist to heavy mechanical strain.
Bisphosphonates belong to a group of pharmaceuticals which has been developed during the last 30 years for diagnostic and therapeutic purposes with regard to bone and calcium metabolic diseases. Some compounds of this type are used in pharmaceuticals for the treatment of osteoporosis. The are approved in Germany for the therapy of osteoporosis in postmenopausal women, osteodystrophia deformans and the hypercalcemia associated with tumors. Furthermore, they are used in the treatment of bone metastases and fibrous dysplasia.
Ongoing research with the aim to find bone specific therapeutics based on bisphosphonates is described in S Zhang, G Gangal, H Uludag: ‘Magic bullets’ for bone diseases: progress in rational design of bone-seeking medicinal agents”, Chem Soc Rev 2007, 36, 507-531. In R S Ehrick, M Capaccio, D A Puleo, L G Bachas: “Ligand-Modified Aminobisphosphonate for Linking Proteins to Hydroxyapatite and Bone Surface”, Bioconjugate Chem 2008, 19, 315-321, a synthesis route to bind tetraethyl(aminomethylene)bisphosphonate (AMB) to biotin, and the binding of AMB biotin to hydroxylapatite.
Methods suitable to coat antimicrobially surfaces with natural product hybrids are described in J-Y Wach, S Bonazzi, K Gademann: “Antimikrobielle Oberflächen durch Naturstoffhybride” (Antimicrobial surfaces due to natural product hybrids), 120, 7232-7235. The natural product hybrids comprise monomeric catecholamines.
Examinations with regard to structure-activity relationships of methylated or hydroxyterminated polyglycerol structures, which were deposited as SAMs on surfaces of gold, are described in M Wyszogrodzka, R Haag: “Study of Single Protein Adsorption onto Monoamino Oligoglycerol Derivatives: A Structure-Activity Relationship”, Langmuir 2009, 25, 5703-5712. The dendritic polyglycerol structures shown do not comprise any bisphosphonates.
In J K Young, G R Baker, G R Newkome: “Smart Cascade Polymers. Modular Syntheses of Four-Directional Dendritic Macromolecules with Acidic, Neutral, or Basic Terminal Groups and the Effect of ph Changeson their Hydrodynamic Radii”, Macromolecules 1994, 27, 3464-3471 are described examples for the synthesis of fourdirectional, flexible and dentritic cascade polymers. The disclosed dendritic molecules, however, do not comprise any bisphosphonate groups.
In K Yoon, P Goyal, M Weck: “Monofunctionalization of Dendrimers with Use of Microwave-Assisted 1,3-Dipolar Cycloadditions”, Org Lett 2007, 9, 2051-2054, are also described methods for the production of flexible dendritic compounds. The work discloses, inter alia, the introduction of cyclic functional groups via 1,3-dipolar cycloadditions. M Kleinert, T Winkler, A Terfort and T B Lindhorst describe in “A modular approach for the construction and modification of glyco-SAMs utilizing 1,3-dipolar cycloaddition”, Org Biomol Chem 2008, 6, 2118-2132 also methods for the modular synthesis of flexible dendritic compounds. In addition to 1,3 dipolar cycloadditions are also described click reactions on SAMs.
Until now, the state of the art does not know a way of bonding bisphosphonates to trivalent flexible skeletons.